慢性冬眠心肌的间质重塑

Interstitial remodeling in a swine model of chronic hibernating myocardium

目的:观察慢性冬眠心肌(CHM)间质变化及其对心功能的影响。方法:对小型猪采用球囊扩张及内膜剥脱术,造成心脏左前降支中段狭窄、心肌慢性缺血,建立CHM模型。24只小型猪被分成:CHM组和假手术组,于模型建立后4周、12周终止实验。心脏切片以HE染色,透射电镜观察组织形态学;以苦味酸天狼星红(PSR)染色,偏光镜观察间质胶原纤维类型和比例;以免疫组化法测定间质糖蛋白、纤维结合蛋白(FN)和骨桥蛋白(OPN);以超声心动图观察左室收缩功能。结果:较之假手术组(1)CHM的间质空间扩大,成纤维细胞增多,胶原增生;(2)CHM的间质胶原容积分数(ICVF)、血管周围胶原容积分数(PCVF)及光密度积分(IOD)、FN和OPN均明显增加,并随时间延长而增加(P<0.01);(3)PSR染色偏光镜观察示CHM组Ⅰ型胶原大量聚集,排列紊乱,Ⅲ型胶原少量,Ⅰ/Ⅲ胶原比例增高;(4)CHM组的左室射血分数(LVEF)、左室短轴缩短率(LVFS)、室壁增厚率(%WT)显著降低(P<0.01);(5)胶原纤维含量与LVFS、LVEF和%WT呈高度负相关(r=-0.754～-0.872,P<0.01)。结论:慢性冬眠心肌出现间质重塑。

Objective： To explore whether there was a progressive remodeling of the interstitium in chronic hibernating myocardium （CHM）. and to determine whether these alterations affect the cardiac function. Methods： Percutaneous balloon coronary inflation and endothelium denudation were used to develop a stenosis of the left anterior descending coronary arteries and then to create a model of CHM in swines. Twenty-four swines were assigned to two groups： Group CHM and group of sham operation （SHAM）. At the end of the study, heart was harvested. Hematoxylin-eo- sin （HE） staining and electron microscopy were used to detect the histological and ultrastructural changes. Picrosiri- us-red staining and polarized light microscopy were conducted to analysis the changes in the type and proportion of collagen fibers. Immunohistochemistry was used to detect two glycoproteins （fibronectin and osteopontin） respectively by their antibodies. Echocardiography was performed to measure the function of the left ventricle. Results： （1） Enlarge- ment of interstitial space, proliferation of fibroblasts, hyperplasia of collagen fibers were observed in group CHM; （2） Compared with group SHAM, both interstitial collagen volume fraction （ICVF）, perivascular collagen volume fraction （PCVF） and IOD of group CHM were significantly increased, and the similar alteration was observed in the expression of two glycoproteins, fibronectin and ostopontin in extracellular matrix （P〈0.01）; （3） A large number of disarranged collagen fibrils of type I with a small amount of type Ⅲ collagen fibers were in interstitium of CHM, accordingly, the ratio of collagen I to collagen Ⅲ increased; （4） Left ventricular fraction shortening （LVFS）, left ventricular ejection fraction （LVEF） and wall thickening （% WT） were significantly lowered in group CHM, respectively （P〈0.01）; （5） Content of collagen fibers were highly negatively correlated with LVFS, LVEF and %WT, respectively （r= -0. 754--0. 872, P〈0.01）. Conclusion： Remodeling of myocardial interstitium are observed in CHM.